Comments on “Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus”

Abstract

W e read with great interest the recent article "Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus" by Khan and colleagues. (1) Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse side effect of antiresorptive agents, and although a significant body of literature has been produced, there remains little evidence-based guidance for clinicians with respect to most aspects of this disease. Therefore, we applaud the attempt of Khan and colleagues to provide a much-needed systematic review.However,itisimportantthatanyreviewonthistopicisaddressed on the basis of the best available evidence and a balanced analysis of the literature. More importantly, systematic reviews require rigorous research methods and a clear and transparent presentation of results in order to limit bias and maximize readability. (2)(3)(4) In the work of Khan and colleagues, (1) we have identified several issues that we suggest carry a risk of affecting the validity of their results.Assessing the risk of bias is a crucial part of systematic reviews. (5,6) Khan and colleagues presented the criteria they used to assign level of evidence and grade recommendations, but unfortunately provided little information regarding qualitative assessment of reviewed studies, related risk of bias, as well as the process of article selection. Overall, it is hard to understand how and why articles were selected or excluded.The presentation of data on incidence and prevalence makes the interpretation of the results difficult. It is well established that incidence data without definition of a time period can be meaningless; (7) nevertheless, results upon incidence of MRONJ are in several instances presented without mentioning the relevant time frame. There are also inconsistencies between different sections of the article: For example, in the abstract, it is stated that "in the osteoporosis patient population MRONJ incidence is estimated at 0.001 to 0.01%," whereas different figures are reported in the results (0.15% to <0.001% personyears of exposure). Furthermore, the authors state that the prevalence of MRONJ in the oncological setting ranges from "0 to 0.186%" whereas the work of Walter and colleagues, which they cite, reports a prevalence of 18.6%. (8) Khan and colleagues report that the incidence of MRONJ in the osteoporosis population would only be "marginally higher than the incidence in the general population," which in the abstract is reported to be <0.001%. (1) This statement is quite

Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology

“…On the other hand, an international task force recently confirms the ASBMR 2007 definition without the AAOMS 2009 and 2014 amends. [32,33] These controversies on definition are clearly of paramount importance as a possible cause of incorrect estimation of ONJ incidence on clinical studies, as well as patient selection and follow-up duration, [34] and they might also induce under-diagnosing of ONJ cases in clinical practice. Furthermore, the purely clinical-based definition of ONJ is questioned by the emergent role of imaging studies.…”

Delayed Diagnosis of Osteonecrosis of the Jaw (ONJ) Associated with Bevacizumab Therapy in Colorectal Cancer Patients: Report of Two Cases

“…Osteonecrosis of the Jaw (ONJ) has been reported in patients treated with bisphosphonates since 2003 [ 1 ]. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) was defined by AAOMS (American Association of Oral Maxillofacial Surgeons) in 2007 as the presence of exposed, necrotic bone in the maxillofacial region that has persisted for more than eight weeks in patients with current or previous treatment with bisphosphonates, and no history of head and neck radiation to the jaws [ 2 ]; however, the occurrence of cases without bone exposure questioned that definition [ 3 , 4 , 5 ].…”

Osteonecrosis of the Jaws (ONJ) after Bisphosphonate Treatment in Patients with Multiple Myeloma: Decreasing ONJ Incidence after Adoption of Preventive Measures

“…In 2014, an AAOMS special committee released a third position paper [ 47 ] changing the term from BRONJ (bisphosphonate-related ONJ) to MRONJ (medication-related ONJ) in order to include cases arising after treatment with denosumab or antiangiogenic drugs and targeted therapies, without BPs; in that document, the definition of disease was enlarged to include cases with “bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region that has persisted for longer than 8 weeks”, but the existence of a “stage 0 category” for patients with signs and symptoms without bone exposure was confirmed. On the other hand, an international task force recently confirmed the 2007 American Society for Bone and Mineral Research (ASBMR) definition without the AAOMS 2009 and 2014 amendments [ 48 , 49 ]. These controversies on definition are clearly of paramount importance as a possible cause of the incorrect estimation of ONJ incidence on clinical studies, as well as patient selection and follow-up duration [ 50 ], and they might also induce under-diagnosing of ONJ cases in clinical practice.…”